U.S. Pat. No. 4,405,792--Walter I--discloses 4-(3-chlorocyclohex-3-enyl)pyridine, 4-(4-chlorocyclohex-3-eny)-pyridine, a process for making these compounds by a Diels-Alder reaction between chloroprene and a 4-vinylpyridine, and a process for converting them to 4-(3-chlorophenyl)pyridine and 4-(4-chlorophenyl)pyridine by catalytic dehydrogenation.
Copending application Ser. No. 495,977, filed May 19, 1983, in the name of Thomas J. Walter--Walter II--discloses processes by which 4-(4-halophenyl)pyridines, such as the 4-chlorophenyl)pyridine produced in Walter I, can be converted to 4-(4-halo-3-nitrophenyl)pyridines, then to 4-(3-aminophenyl)pyridines, and ultimately to the antibacterial 1-alkyl-1,4-dihydro-4-oxo-7-pyridinyl-3-quinolinecarboxylic acids of Sterling Drug's U.S. Pat. Nos. 3,753,993 (Lesher et al.), 3,907,808 (Lesher and Carabateas), and 4,118,557 (Lesher).
Separately and in combination, the aforementioned copending applications disclose useful processes for preparing antibacterial agents and intermediates thereof. However, as indicated by the working examples of Walter I, it has not previously been known how to conduct a Diels-Alder reaction between chloroprene and 4-vinylpyridine, or homologs thereof, so as to get satisfactory yields of 4-(chlorocyclohex-3-enyl)pyridines. The side reactions that have occurred in the reaction, specifically the polymerization of the chloroprene and the dimerization of the 4-vinylpyridine, have reduced the yield to not more than about 20-30% of 4-(chlorocyclohex-3-enyl)pyridine isomers in a 65:35 mol ratio of 4-(4-chlorocylohex-3-enyl)pyridine to 4-(3-chlorocyclohex-3-enyl)-pyridine.
W. Carruthers, Some modern methods of organic synthesis, Second Edition, Cambridge University Press, 1978, page 198, shows that previous attempts to catalyze Diels-Alder reactions have generally met with little success but that some Diels-Alder reactions have been found to be accelerated remarkably by aluminum chloride and other Lewis acids. J. Sauer, "Diels-Alder Reactions II: The Reaction Mechanism," Angewandte Chemie international Edition, Volume 6, No. 1, 1967, pages 16-33, teaches that the acceleration of Diels-Alder reactions by Lewis acids, including boron trifluoride, can be considerable in some cases (page 28), that the ratio of stereoisomers produced by the reaction can be affected by the use of Lewis acids (page 19), and that the ratio of position isomers can also be affected (page 24).
It would be advantageous to be able to modify Diels-Alder reactions between haloprenes and 4-vinylpyridines so as to produce satisfactory yields of Diels-Alder adducts and concurrently to maximize the yield of the isomers most desirable for the production of the aforementioned antibacterial agents, i.e., the 4-(4-halocyclohex-3-enyl)pyridine isomers.